The program Project entitled Neurobiology of Mild Cognitive Impairment in the Elderly is entering its eleventh year. The overall goal of the project is the determine the molecular substrate of the onet of cognitive decline in eldery people with mild cognitive impairment prior to the development of frant Alzheimer's disease. To accomplish this goal the program brings together a number of basic and clinical scientists from the Chicago area and outside universities. The project will be based at Rush University Medical Center in Chicago. The Program Project consists of an Administrative and Tissue distribution Core and a Statistics and Data Management Core. In addition the following four research projects complete the program: 1: Neurofibrillary Tangle Evolution in Mild Cognitive Imapairment (Lester Skip Binder, Northwestern University Medical Center, project leader); 2) LR11 in Mild Cognitive Impairment (Allan Levey, Emory University, project leader); 3) Cholinotrophic Abnormalities and Mild Cognitive Impairment (Elliott Mufson, Project Leader); and 4) Synaptic, Cholinergic and Amyloid Abnormalities and Mild Cognitive impairment (Steven DeKosky, University of Pittsburgh project 1 Leader). Each core will support all of these research projects. Moreover, these projects will receive clinical data and tissue samples from the NIA funded Rush ADCC Neuropahtology and Religious Orders Study Cores for all projects. The results of the data produced by the Program Project will shed new light on the neurobiology of elderly people with mild cognitive impairmnent, the transistion to AD and are will facilitate the translational development of stage-specific therapies for AD.